OTOTOXIC EFFECTS OF SUPRADOSE CISPLATIN WITH SODIUM THIOSULFATE NEUTRALIZATION IN PATIENTS WITH HEAD AND NECK-CANCER

Objective: To assess the incidence and magnitude of ototoxicity in pat ients undergoing an experimental targeted chemoradiation protocol inco rporating extremely high-dose intra-arterial cisplatin therapy with sy stemic sodium thiosulfate neutralization for the treatment of advanced carcinomas of the head and neck. Design: inception cohort study. Sett ing: University-based, tertiary care referral center for advanced head and neck malignant disease. Patients: The first 70 patients with adva nced carcinomas of the head and neck consecutively entered in the prot ocol. Intervention: Patients received up to 4 weekly courses of intra- arterial cisplatin (150 mg/m(2) per infusion), together with systemic sodium thiosulfate and external beam radiation (68-70 Gy). Audiometric analysis was performed before the initiation of therapy, and subseque nt to the second and fourth cisplatin infusions. Main Outcome Measures : Audiometric thresholds. Ototoxicity was defined as an increase in pu re-tone threshold of 15 dB at 1 frequency or 10 dB at 3 frequencies, b etween 250 and 4000 Hz. Results: The incidence of ototoxicity was 25% at 150 mg/m(2), 50% at 300 mg/m(2), 64% at 450 mg/m(2), and 60% at 600 mg/m2. Hearing at frequencies of 2000 Hz or less was minimally or not affected. Previous hearing loss did not appear to affect the incidenc e of ototoxicity. A plateau of hearing loss at 60-dB hearing level, as noted by other authors, was not observed. There were no cases of debi litating tinnitus or of vestibular loss. Conclusions: Ototoxicity did occur but was largely confined to the higher frequencies. Hearing loss es resulting from this chemoradiation protocol were not sufficiently s evere to alter its application.